Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”

Within a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To facilitate such studies, we recently devel...

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Main Authors: Michael Meadow, Sarah Broas, Margaret Hoare, Maria Ahmed, Fatemeh Alimohammadi, Kevin Welle, Kyle Swovick, Jennifer Hryhorenko, Anushka Jain, John Martinez, Andrei Seluanov, Vera Gorbunova, Abigail Buchwalter, Sina Ghaemmaghami
Format: Article
Language:English
Published: Bio-protocol LLC 2025-05-01
Series:Bio-Protocol
Online Access:https://bio-protocol.org/en/bpdetail?id=5296&type=0
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author Michael Meadow
Sarah Broas
Margaret Hoare
Maria Ahmed
Fatemeh Alimohammadi
Kevin Welle
Kyle Swovick
Jennifer Hryhorenko
Anushka Jain
John Martinez
Andrei Seluanov
Vera Gorbunova
Abigail Buchwalter
Sina Ghaemmaghami
author_facet Michael Meadow
Sarah Broas
Margaret Hoare
Maria Ahmed
Fatemeh Alimohammadi
Kevin Welle
Kyle Swovick
Jennifer Hryhorenko
Anushka Jain
John Martinez
Andrei Seluanov
Vera Gorbunova
Abigail Buchwalter
Sina Ghaemmaghami
author_sort Michael Meadow
collection DOAJ
description Within a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To facilitate such studies, we recently developed a technique termed “proteome birthdating” that differentially labels proteins based on their time of synthesis. Proteome birthdating enables analyses of age distributions of the proteome by tandem mass spectrometry (LC–MS/MS) and provides a methodology for investigating the protein age selectivity of diverse cellular pathways. Proteome birthdating can also provide measurements of protein turnover kinetics from single, sequentially labeled samples. Here, we provide a practical guide for conducting proteome birthdating in in vitro model systems. The outlined workflow covers cell culture, isotopic labeling, protein extraction, enzymatic digestion, peptide cleanup, mass spectrometry, data processing, and theoretical considerations for interpretation of the resulting data.
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institution Kabale University
issn 2331-8325
language English
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publisher Bio-protocol LLC
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spelling doaj-art-8d2cd747d7224629844f042d7b83a3bf2025-08-20T03:48:46ZengBio-protocol LLCBio-Protocol2331-83252025-05-0115910.21769/BioProtoc.5296Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”Michael Meadow0Sarah Broas1Margaret Hoare2Maria Ahmed3Fatemeh Alimohammadi4Kevin Welle5Kyle Swovick6Jennifer Hryhorenko7Anushka Jain8John Martinez9Andrei Seluanov10Vera Gorbunova11Abigail Buchwalter12Sina Ghaemmaghami13Department of Biology, University of Rochester, NY, USAMedical Scientist Training Program, University of Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USAUniversity of Rochester Mass Spectrometry Resource Laboratory, NY, USAUniversity of Rochester Mass Spectrometry Resource Laboratory, NY, USAUniversity of Rochester Mass Spectrometry Resource Laboratory, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Medicine, University of Rochester Medical Center, Rochester, NY, USADepartment of Biology, University of Rochester, NY, USADepartment of Medicine, University of Rochester Medical Center, Rochester, NY, USACardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USADepartment of Biology, University of Rochester, NY, USAUniversity of Rochester Mass Spectrometry Resource Laboratory, NY, USAWithin a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To facilitate such studies, we recently developed a technique termed “proteome birthdating” that differentially labels proteins based on their time of synthesis. Proteome birthdating enables analyses of age distributions of the proteome by tandem mass spectrometry (LC–MS/MS) and provides a methodology for investigating the protein age selectivity of diverse cellular pathways. Proteome birthdating can also provide measurements of protein turnover kinetics from single, sequentially labeled samples. Here, we provide a practical guide for conducting proteome birthdating in in vitro model systems. The outlined workflow covers cell culture, isotopic labeling, protein extraction, enzymatic digestion, peptide cleanup, mass spectrometry, data processing, and theoretical considerations for interpretation of the resulting data.https://bio-protocol.org/en/bpdetail?id=5296&type=0
spellingShingle Michael Meadow
Sarah Broas
Margaret Hoare
Maria Ahmed
Fatemeh Alimohammadi
Kevin Welle
Kyle Swovick
Jennifer Hryhorenko
Anushka Jain
John Martinez
Andrei Seluanov
Vera Gorbunova
Abigail Buchwalter
Sina Ghaemmaghami
Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
Bio-Protocol
title Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
title_full Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
title_fullStr Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
title_full_unstemmed Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
title_short Proteome Birthdating: A Single-Sample Approach for Measuring Global Turnover Dynamics and “Protein Age”
title_sort proteome birthdating a single sample approach for measuring global turnover dynamics and protein age
url https://bio-protocol.org/en/bpdetail?id=5296&type=0
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